Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria  -  Lancet Volume 354, Number 9176 31 July 1999
Piero Ruggenenti, etc. Mario Negri Institute for Pharmacological Research, Clinical Research Centre for Rare Diseases Italy

Background
Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h.  

Methods
In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (3 g/24 h). Median follow-up was 31 months.

Findings
The decline in GFR per month was not significantly different (ramipril 0·26 [SE 0·05] mL per min per 1·73m2, control 0·29 [0·06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2·72 (95% CI 1·22-6·08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2·40 [1·27-4·52]). Patients with a baseline GFR of 45 mL/min/1·73 m2 or less and proteinuria of 1·5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2.

Interpretation
In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.

Lancet 1999; 354: 359-64